The Mediating Role of Emotion Dysregulation in the Association Between Perfectionism and Eating Psychopathology Symptoms.

INTRODUCTION: This study explored the possible mediating role of emotion dysregulation in the association between perfectionism and eating psychopathology symptoms. METHOD: One hundred forty-two outpatients with eating disorders (EDs) were enrolled. Perfectionism, emotion dysregulation, ED psychopathology, anxious and depressive symptoms were assessed. Correlation, mediation and 95% bias corrected and accelerated (BCa CI) bootstrapped analyses were run. RESULTS: Emotion dysregulation was found to mediate the association between concern over mistakes perfectionism and restraint (indirect effect: 0.093, BCa CI: 0.001-0.02, adjusted R2 = 0.3324, p < 0.001), shape concern (indirect effect: 0.0130, BCa CI: 0.004-0.03, adjusted R2 = p < 0.001) and weight concern (indirect effect: 0.0142, BCa CI: 0.004-0.03, adjusted R2 = 0.2986, p < 0.001). CONCLUSION: Among ED outpatients, emotion dysregulation may be involved in the association between concern over mistakes perfectionism and persistence of eating psychopathology symptoms. Emotion dysregulation could be considered as possible therapeutic target to reduce the persistence, and severity, of eating psychopathology symptoms among ED patients with concern over mistakes perfectionism.

The Metacognitions about Binge Eating Questionnaire: Investigation of the association between specific metacognitions and Binge Eating Disorder.

Literature suggested that metacognitions are involved in eating problems and may be relevant to the understanding of Binge Eating Disorder (BED). The goal of the current studies was to develop the first self-report instrument on metacognitions about binge eating. In Study 1, a community sample completed the Metacognitions about Binge Eating Questionnaire (MBEQ); an Exploratory Factor Analysis (EFA) was performed. In study 2, a community sample completed the MBEQ and measures assessing severity of binge eating, irrational food beliefs, anxiety, depression, impulsiveness. A Confirmatory Factor Analysis (CFA) was performed. Concurrent and incremental validity were assessed. In study 3, a clinical sample of participants with a diagnosis of BED completed the MBEQ and other measures. Bivariate correlational analysis and hierarchical linear regression were performed. Participants from the general population and participants with a diagnosis of BED were compared. EFA and CFA supported a two-factor solution consisting of positive and negative metacognitions about binge eating. Concurrent and incremental validity were acceptable. The metacognitions factors correlated positively with anxiety, depression, irrational food beliefs, impulsiveness in the community sample, and anxiety, irrational food beliefs, impulsiveness in clinical sample. The metacognitions factors contributed to the prediction of BEDs symptoms, in community and clinical samples, over and above age, gender, impulsiveness, anxiety, depression, irrational food beliefs. The MBEQ possesses good psychometric properties and appears a reliable and valid measure of positive and negative metacognitions about binge eating. Metacognitions about binge eating could be a therapeutic target to reduce the severity of binge eating episodes.

Psychometric validation of the desire thinking questionnaire in a Turkish adolescent sample: Associations with internet gaming disorder.

BACKGROUND: Desire thinking is a conscious and voluntary cognitive process that consists of perseverative focus on information, memories, and prefiguration of images related to a desired target. The Desire Thinking Questionnaire (DTQ) is acknowledged as a reliable and valid tool to measure desire thinking in both adults and adolescents. The aim of the present study was to examine the psychometric properties of the DTQ in Turkish adolescent sample. METHODS: A convenience sample of 200 adolescents completed the Turkish version of the DTQ (DTQ-T) and an Exploratory Factor Analysis (EFA) was performed. Subsequently, a convenience sample of 701 adolescents completed the DTQ-T and a battery of questionnaires assessing personality traits, affect, boredom, impulsivity, and Internet Gaming Disorder (IGD). A Confirmatory Factor Analysis (CFA) was performed on the DTQ-T and validity was determined by examining correlations with other measures. RESULTS: A 9-item two-factor structure was observed in the EFA. An 8-item two-factor structure was established in the CFA. Results demonstrated that the DTQ-T yields adequate levels of reliability and concurrent validity. Additionally, an examination of incremental validity showed that DTQ-T significantly predicted IGD when controlling for personality traits, affect, boredom, and impulsivity. CONCLUSIONS: The 8-item DTQ-T was found to be a reliable and valid measure of desire thinking among Turkish adolescents. Desire thinking may be a feasible target for mental health workers to alleviate the symptoms of IGD.

The importance of thinking styles in predicting binge eating.

Impulsivity, Body Mass Index, negative emotions and irrational food beliefs are often reported as predictors of binge eating. In the current study we explored the role played by two thinking styles, namely food thought suppression and desire thinking, in predicting binge eating among young adults controlling for established predictors of this condition. A total of 338 university students (268 females) participated in this study by completing a battery of questionnaires measuring the study variables. Path analysis revealed that impulsivity was not associated with binge eating, that Body Mass Index and negative emotions predicted binge eating, and that irrational food beliefs only influenced binge eating via food thought suppression and desire thinking. In conclusion, thinking styles appear an important predictor of binge eating and they should be taken into consideration when developing clinical interventions for binge eating.

The novel anti-inflammatory agent VA694, endowed with both NO-releasing and COX2-selective inhibiting properties, exhibits NO-mediated positive effects on blood pressure, coronary flow and endothelium in an experimental model of hypertension and endothelial dysfunction.

Selective cyclooxygenase 2 (COX2) inhibitors (COXIBs) are effective anti-inflammatory and analgesic drugs with improved gastrointestinal (GI) safety compared to nonselective nonsteroidal anti-inflammatory drugs known as traditional (tNSAIDs). However, their use is associated with a cardiovascular (CV) hazard (i.e. increased incidence of thrombotic events and hypertension) due to the inhibition of COX2-dependent vascular prostacyclin. Aiming to design COX2-selective inhibitors with improved CV safety, new NO-releasing COXIBs (NO-COXIBs) have been developed. In these hybrid drugs, the NO-mediated CV effects are expected to compensate for the COXIB-mediated inhibition of prostacyclin. This study evaluates the potential CV beneficial effects of VA694, a promising NO-COXIB, the anti-inflammatory effects of which have been previously characterized in several in vitro and in vivo experimental models. When incubated in hepatic homogenate, VA694 acted as a slow NO-donor. Moreover, it caused NO-mediated relaxant effects in the vascular smooth muscle. The chronic oral administration of VA694 to young spontaneously hypertensive rats (SHRs) significantly slowed down the age-related development of hypertension and was associated with increased plasma levels of nitrates, stable end-metabolites of NO. Furthermore, a significant improvement of coronary flow and a significant reduction of endothelial dysfunction were observed in SHRs submitted to chronic administration of VA694. In conclusion, VA694 is a promising COX2-inhibiting hybrid drug, showing NO releasing properties which may mitigate the CV deleterious effects associated with the COX2-inhibition.

Targeting of ADAMTS5's ancillary domain with the recombinant mAb CRB0017 ameliorates disease progression in a spontaneous murine model of osteoarthritis.

OBJECTIVE: ADAMTS5 (aggrecanase-2) has been demonstrated to be crucial in the development of osteoarthritis (OA), by use of several mouse mutants carrying either truncated, catalytically inactive enzymes or aggrecanase-resistant mutant aggrecan. We have selected recombinant monoclonal antibodies directed against ADAMTS5, by using Intracellular Antibody Capture Technology (IACT). CRB0017 revealed very high affinity for the enzyme in Biacore analyses and very good specificity in a panel of binding assays. Therefore, we tested CRB0017 in a relevant spontaneous OA model, the STR/ort mouse. DESIGN: STR/ort male mice were recruited at 5 months of age, and treated intra-articularly in each knee with CRB0017 1.2 µg, CRB0017 12 µg, or vehicle. After 6 weeks, the intra-articular administration of CRB0017 was repeated with the same doses. After 3 months from recruitment, the animals were sacrificed and the femorotibial joints processed for histology and scored in a blind fashion according to both Mankin's and the OARSI methods. RESULTS AND CONCLUSIONS: All histological scores were significantly decreased in the CRB0017 12 µg/knee group compared to vehicle, while administration of CRB0017 1.2 µg was associated with a trend to a decrease in the same parameters. Therefore, CRB0017 administered twice in 3 months could modify the course of OA in the STR/ort mouse, by delaying cartilage breakdown as assessed histologically. The procedure of blind scoring of the histological samples clearly showed that knee intra-articular administration of CRB0017, an anti-ADAMTS5 antibody, dose-dependently improved disease progression in a relevant animal model of OA.

Thrombin injection and compression with removable guidewire in the treatment of postcatheterization femoral pseudoaneurysm.

AIM:The purpose of our study was to determine the efficacy of percutaneous thrombin treatment for iatrogenic femoral artery pseudoaneurysms (FAP) and to identify those criteria that may help to predict increased treatment failure risk and complications. METHODS: A number of 32 iatrogenic femoral pseudoaneurysms were treated with US-guided thrombin injection (group A), while four elderly patient with complex femoral pseudoaneurysm underwent compression assisted by removable "guidewire" (group B). Twenty-five were classified as simple (single lobe) and 11 as complex (at least two lobes with a single neck to the native vessel). Pseudoaneurysm volume, classification, thrombin dose, anticoagulation therapy status, and sheath size were considered independent prognostic factors. RESULTS: All the 36 patients (pts) had initial complete femoral pseudoaneurysms thrombosis. The aneurysm was thrombosed on a Doppler ultrasound (US) follow-up in all the cases but four (group A), those who required the additional thrombin injection. A fatal complication occurred in one patient with complex FAP (group A). CONCLUSION: Preliminary data suggest that US-guided percutaneous thrombin injection is a safe and effective method to treat iatrogenic pseudoaneurysms. Simple iatrogenic femoral pseudoaneurysms benefit a single injection of up to 500 units of topical thrombin. We recommend more caution in complex pseudoaneurysms treatment; it is preferable to perform thrombin injection first into the lobe which is not directly joined to the femoral artery. A longer bed rest and closer observation are mandatory during the subsequent 24 hours. If the lobe communicating with the femoral artery is still patent, it can be retreated. Alternatively, we propose a new strategy approach through compression assisted removable "guidewire".

Pulmonary emboli due to venous aneurysm of extremities.

Venous aneurysms are uncommon but they can have devastating consequences, including pulmonary embolism, other thromboembolic events and death. We report six cases of venous aneurysm of the extremities, in which the first sign of presence was acute pulmonary embolism. Surgical resection is recommended whenever possible. Our experience suggests that prophylactic surgery is cautiously recommended for low-risk patients with venous aneurysms of the abdomen and strongly recommended for extremity deep and superficial venous aneurysms for their potential risk of developing thromboembolic complications despite adequate anticoagulation. Other venous aneurysms should be excised only if they are symptomatic or enlarging.

Fatal complication after thrombin injection for post-catheterization femoral pseudoaneurysm.

Femoral artery pseudoaneurysm (FAP) is one of the most common vascular complications after cardiac and peripheral angiographic procedures. Ultrasound-guided thrombin injection is the standard procedure for the treatment of FAP. Complications such as thrombotic events with leg ischemia after thrombin leakage into the femoral artery or immunogenic consequences are rare. Our experience indicates the need for caution when treating FAP, as severe complications can occur after thrombin injection in a femoral pseudoaneurysm, leading to a fatal event.

Surgical removal of a ruptured, detached angioplasty balloon after popliteal stenting.

Balloon catheter entrapment after stent implantation is a potential interventional complication. However, angioplasty balloon disconnection from the catheter shaft and in-stent entrapment is a very uncommon event that could have serious thrombotic or embolic consequences. The management of this event may be interventional or surgical, depending on the patient's status and the position of the balloon inside the vessel. We describe a case of acute lower limb ischemia after popliteal self-expandable stenting, due to loss of the balloon along with a portion of its shaft. Surgical retrieval was accomplished without any further complications.

Andolast acts at different cellular levels to inhibit immunoglobulin E synthesis.

The anti-asthmatic agent andolast is thought to inhibit the release of allergic mediators, but its mechanism of action is not fully understood. We investigated whether the compound inhibits immunoglobulin E (IgE) synthesis and tested the hypothesis that andolast affects immunoglobulin class switching. Interleukin (IL)-4 and the interaction of CD40 expressed on B cells with its ligand on T cells are necessary for IgE synthesis. Thus, peripheral blood mononuclear cells (PBMCs) from 40 asthmatic, 16 non-asthmatic allergic, and 9 normal donors were stimulated with IL-4 and/or anti-CD40 antibody. T cells from 9 additional allergic donors were activated with anti-CD3/CD28 antibodies to express IL-4 mRNA. After incubation in the absence or presence of test compounds, immunoglobulin concentrations were measured by enzyme immunoassay, and mRNA levels were analyzed by RT-PCR. Andolast significantly inhibited IgE synthesis by stimulated PBMCs from both asthma patients and combined allergic/normal donors. In mechanistic studies, andolast was found to act at different cellular levels. Firstly, it reduced by about 45 percent (p<0.05) the levels of IL-4 mRNA in T cells stimulated with anti-CD3/CD28. Secondly, andolast reduced by about 36 percent (p<0.05) the expression of epsilon germline transcripts in PBMCs stimulated with IL-4/anti-CD40. Thirdly, the effect of andolast on immunoglobulin synthesis was selective in that the production of IgG4 antibodies was not significantly inhibited. Our findings, while supporting the evidence that andolast is effective for the treatment of asthma, provide new insights into its mechanism of action.

Glutamate signaling in chondrocytes and the potential involvement of NMDA receptors in cell proliferation and inflammatory gene expression.

OBJECTIVE: Increased levels of glutamate, the main excitatory neurotransmitter, are found in the synovial fluid of osteoarthritis (OA) patients. Our aim was to study glutamate signaling in chondrocytes, focusing on the composition, pharmacology, and functional role of N-methyl-d-aspartate (NMDA) glutamate receptors. METHODS: We used the human chondrocyte cell line SW1353 and, in parallel, primary rat articular chondrocytes. Glutamate release and uptake were measured by fluorimetric and radiometric methods, respectively. Gene expression was analyzed by quantitative polymerase chain reaction. NMDA receptor pharmacology was studied in binding experiments with [3H]MK-801, a specific NMDA receptor antagonist. RNA interference was used to knock-down the expression of NR1, a subunit of NMDA receptors. RESULTS: Glutamate release, sodium- and calcium-dependent glutamate uptake, and the expression of a glutamate transporter were observed in chondrocytes. NR2D was the most abundant NMDA receptor subunit in these cells. Consistent with this observation, the binding affinity of [3H]MK-801 was much lower in chondrocytes than in rat brain membranes (mean K(d) values of 700 and 2.6 nM, respectively). NR1 knock-down, as well as NMDA receptor blockade with MK-801, reduced chondrocyte proliferation. Interleukin (IL)-1beta significantly altered glutamate release and uptake (about 90% increase and 50% decrease, respectively, in SW1353 cells). Moreover, IL-1beta induced the gene expression of cytokines and enzymes involved in cartilage degradation, and MK-801 significantly inhibited this response. CONCLUSIONS: Our findings suggest that chondrocytes express a self-sufficient machinery for glutamate signaling, including a peripheral NMDA receptor with unique properties. This receptor may have a role in the inflammatory process associated with cartilage degradation, thus emerging as a potential pharmacological target in OA.

Pharmacokinetic study of a new angiotensin-AT1 antagonist by HPLC.

Recently an innovative novel class angiotensin-AT1 antagonist has been developed by Rottapharm. In this study, we present a validated method for detecting CR 3834 in biological matrices using high-performance liquid chromatography (HPLC) with diode array detection. After oral administration (30mg/kg) to Wistar rats, the plasma and urine concentrations of CR 3834 and its potential metabolic products were determined. Moreover, the plasmatic time course in rats has been determined after intravenous (IV) administration of CR 3834 (5mg/kg). Biological samples (0.5ml of plasma and 1ml of urine) were purified using solid-phase extraction (SPE) of analytes and the internal standard Idebenone, 2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1-4-benzoquinone. A chromatographic separation was performed on an Adsorboshere C18 at 25 degrees C, with a pre-column of the same matrix; the eluent was made up of acetonitrile/acidified water with CF3COOH (pH 2.01) in ratio of 75:25 (v/v); the flow rate was 1.0ml/min and a 100microl loop. The lower limit of detection (LOD) was taken as 25ng/ml in plasma and 50ng/ml in urine samples. The lower limit of quantification (LOQ) was taken as 0.1 and 0.2microg/ml in plasma and urine samples, respectively. The procedures were validated according to international standards with a good reproducibility and linear response (r=0.9916 in plasma; r=0.9997 in urine). The coefficients of variation inter assay ranged between 2.579 and 4.951% in plasma, and between 0.813 and 2.460% in urine. Mean recovery for CR 3834 was 79% in plasma and 97% in urine samples. The experiments performed demonstrated that the method presented was suitable for determining this new angiotensin-AT1 antagonist in rat plasma and urine.

Pituitary height and neuroradiological alterations in patients with Prader-Labhart-Willi syndrome.

Prader-Willi syndrome (PWS), a genetic disorder due to an alteration in the paternally derived long arm of chromosome 15, is characterized by a complex clinical picture (short stature, obesity, hypogonadism) that seems to be referable to as a central hypothalamic/pituitary dysfunction. To determine whether there is any diminution in the anterior pituitary gland or other neuroradiological alterations, we retrospectively analysed 91 patients with PWS (42 females, 49 males; age range: 0.7-16.8 years) by cerebral magnetic resonance imaging (MRI). Of these 91 patients, MRI analysis showed a reduction in pituitary height in 45 patients (49.4%), a complete absence of the posterior pituitary bright spot in six patients (6.6%) and other neuroradiological alterations in ten patients (11%). Altogether, neuroradiological alterations were present in 61 of the 91 (67%) patients. Our results indicate that neuroradiological alterations are more frequent in PWS patients than has been reported to date.

Albright's hereditary osteodystrophy (pseudohypoparathyroidism type Ia): clinical case with a novel mutation of GNAS1.

Albright's hereditary osteodystrophy is characterized by ectopic calcification and ossification, round face, short hands and feet with short terminal phalanges, short metacarpals (especially 4th and 5th) and absence of the 4th knuckle (brachydactyly type E). Here we describe a case that recently came to our attention of a girl suffering from seizures caused by hypocalcaemia, in which the clinical diagnosis of Albright's hereditary osteodystrophy and Pseudohypoparathyroidism (PHP) (Pseudohypoparathyroidism Ia) was confirmed by DNA molecular analysis. This analysis revealed a novel mutation of GNAS 1, resulting in the nonsense mutation of exon 13 (CAG-->TAG, codon 384). This result expands the spectrum of GNAS1 mutations associated with this disorder.

Dermatological marks in athletes of artistic and rhythmic gymnastics.

The authors present dermatological signs in: a) rhythmic gymnastics athletes, b) male artistic gymnastics athletes, compared to a control group of fitness athletes. Athletes from the artistic gymnastics group were observed twice. The signs they showed on their first examination (20 days previous to the competition) were two circular zones of thickening of the skin with relation to the radial epiphysis. In all of them, two zones of frictional alopecia were present, one on the dorsal face of the forearms, slantwise outlined, the other on the wrists. A noticeable thickening of the skin was present on the palms of the hands. On a second examination, at the beginning of the training, after about two months of inactivity, the alopecic area was replaced by hypertrichosis, although featuring different patterns in each athlete. Thickening of the skin was slightly smaller than that observed at the first examination. The authors describe onychopathology shown in its different forms in 94 % of the athletes of the rhythmic group. Subsequently the authors discuss the pathogenesis of the above described signs.

Solitary median maxillary central incisor syndrome: clinical case with a novel mutation of sonic hedgehog.

Solitary median maxillary central incisor (SMMCI) is a rare dental anomaly. It is usually considered as a minor manifestation of holoprosencephaly (HPE). Some reported families had severe cases of HPE in some members and SMMCI in others. Mutations of Sonic Hedgehog (SHH) have been documented in these families. SMMCI has also been found as an isolated finding or together with other anomalies such as microcephaly, short stature, endocrine pathology, and choanal atresia. We describe a patient with SMMCI and a novel SHH mutation: Val332Ala.

In vitro permeation screening of a new formulation of thiocolchicoside containing various enhancers.

Thiocolchicoside, a muscle relaxant agent with anti-inflammatory and analgesic actions, also is used topically for the treatment of muscular spasms and for rheumatologic, orthopedic, and traumatologic disorders. In this study, thiocolchicoside was formulated to use as foam to avoid contact with the afflicted area during the spreading phase. To enhance drug penetration, various enhancers were added to the base formulation. The tested enhancers were ethoxyethylendiglycol (Transcutol), highly purified phosphatidylcholine (Lipoid S20), capsaicin, propylene glycol dipelargonate (DPPG), and glycolysed ethoxylated glycerides (Labrafil M1944 CS). The transdermal absorption of the tested formulations containing enhancers, in comparison with base formulation, was evaluated in vitro through rat skin using standard Franz diffusion cells. Base formulation was found to have a higher permeation profile than the simple aqueous and hydroalcoholic solutions of the drug, meaning that the base formulation by itself enhances the drug permeation. Among the tested formulations, only the formulation containing DPPG/ethanol was found to be statistically different, showing an enhancement factor of 3.58. In the same experimental session, Muscoril ointment, the commercially available pharmaceutical product containing the same thiocolchicoside concentration (0.25%), also was tested. The formulation containing DPPG/ethanol showed a 4.86 times increase of permeability constant in comparison with Muscoril ointment. The formulation containing DPPG/ethanol as an enhancer could be a good candidate for a new topical foam, considering its good characteristics of permeability and compliance.

Role of tumor necrosis factor-alpha in endotoxin-induced lung parenchymal hyporesponsiveness in mice.

Although changes in airway responsiveness in pulmonary inflammation are commonly related to the action of infiltrated leukocytes, our previous report suggested a direct role of inflammatory cytokines in LPS-induced lung hyporesponsiveness. The aim of this study was to define if cytokines detected in the BALF (bronchoalveolar lavage fluid) of intratracheal LPS-treated mice could be, at least in part, responsible for 5-HT (5-hydroxytryptamine) lung hyporeactivity. Our results show that intratracheal instillation of LPS induced a time-dependent increase in IL-(interleukin-)1beta, IL-6, and TNF (tumor necrosis factor)alpha in the BALF. Cytokine production was paralleled by 5-HT lung hyporesponsiveness, and intratracheal administration of TNFalpha proved to be very efficient in inhibiting 5-HT responsiveness. In addition, systemic treatment with rolipram, an inhibitor of TNFalpha production, was paralleled by a significant recovery of lung responsiveness. On the contrary, IL-1beta and IL-6 were not demonstrated to play a relevant role in 5-HT hyporesponsiveness. It is concluded that TNFalpha could be a crucial mediator of LPS-induced lung hyporesponsiveness.

Nodular macroglossia with combined light chain and beta-2 microglobulin deposition in a long-term dialysis patient.

We describe a case in which nodular macroglossia, a very rare type of tongue involvement, was associated with the co-deposition of lambda light chain and beta-2 microglobulin fibrils in the tongue. The combined presence of two different amyloid fibrils did not lead to a more unfavourable clinical outcome. We believe that both these features often remain underdiagnosed and are in fact more frequent than reported. A careful clinical examination of the tongue together with serum immunofixation should be routine in all patients with dialysis-related amyloidosis in order to investigate the prevalence and type of tongue involvement and to rule out other types of amyloidosis. In all cases of suspected mixed amyloidosis, immunohistochemical characterization of fibrils should be carried out by electron microscopy.